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Biomolecules Sep 2019Pyrrolnitrin (PRN) is a microbial pyrrole halometabolite of immense antimicrobial significance for agricultural, pharmaceutical and industrial implications. The compound... (Review)
Review
Pyrrolnitrin (PRN) is a microbial pyrrole halometabolite of immense antimicrobial significance for agricultural, pharmaceutical and industrial implications. The compound and its derivatives have been isolated from rhizospheric fluorescent or non-fluorescent pseudomonads, and . They are known to confer biological control against a wide range of phytopathogenic fungi, and thus offer strong plant protection prospects against soil and seed-borne phytopathogenic diseases. Although chemical synthesis of PRN has been obtained using different steps, microbial production is still the most useful option for producing this metabolite. In many of the plant-associated isolates of and , production of PRN is dependent on the quorum-sensing regulation that usually involves N-acylhomoserine lactone (AHL) autoinducer signals. When applied on the organisms as antimicrobial agent, the molecule impedes synthesis of key biomolecules (DNA, RNA and protein), uncouples with oxidative phosphorylation, inhibits mitotic division and hampers several biological mechanisms. With its potential broad-spectrum activities, low phototoxicity, non-toxic nature and specificity for impacts on non-target organisms, the metabolite has emerged as a lead molecule of industrial importance, which has led to developing cost-effective methods for the biosynthesis of PRN using microbial fermentation. Quantum of work narrating focused research efforts in the emergence of this potential microbial metabolite is summarized here to present a consolidated, sequential and updated insight into the chemistry, biology and applicability of this natural molecule.
Topics: Antifungal Agents; Burkholderia; Fermentation; Fungi; Microbial Sensitivity Tests; Pseudomonas; Pyrrolnitrin; Serratia
PubMed: 31484394
DOI: 10.3390/biom9090443 -
Natural Product Reports Apr 2000
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Microbiological Research Oct 2018Fusarium graminearum is the major causal agent of Fusarium head blight (FHB) disease in cereal crops worldwide. Infection with this fungal phytopathogen can regularly...
Fusarium graminearum is the major causal agent of Fusarium head blight (FHB) disease in cereal crops worldwide. Infection with this fungal phytopathogen can regularly cause severe yield and quality losses and mycotoxin contamination in grains. In previous other studies, one research group reported that pyrrolnitrin had an ability to suppress of mycelial growth of F. graminearum. Other groups revealed that phenazine-1-carboxamide, a derivative of phenazine-1-carboxylic acid, could also inhibit the growth of F. graminearum and showed great potentials in the bioprotection of crops from FHB disease. In our recent work with Pseudomonas chlororaphis strain G05, however, we found that although the phz operon (phenazine biosynthetic gene cluster) was knocked out, the phenazine-deficient mutant G05Δphz still exhibited effective inhibition of the mycelial growth of some fungal phytopathogens in pathogen inhibition assay, especially including F. graminearum, Colletotrichum gloeosporioides, Botrytis cinerea. With our further investigations, including deletion and complementation of the prn operon (pyrrolnitrin biosynthetic gene cluster), purification and identification of fungal compounds, we first verified that not phenazines but pyrrolnitrin biosynthesized in P. chlororaphis G05 plays an essential role in growth suppression of F. graminearum and the bioprotection of cereal crops against FHB disease.
Topics: Bacterial Proteins; Botrytis; Colletotrichum; Crops, Agricultural; Edible Grain; Fungicides, Industrial; Fusarium; Gene Expression Regulation, Bacterial; Gene Knockout Techniques; Genes, Fungal; Multigene Family; Mutation; Mycelium; Operon; Pest Control, Biological; Phenazines; Plant Diseases; Pseudomonas chlororaphis; Pyrrolnitrin
PubMed: 30172309
DOI: 10.1016/j.micres.2018.06.008 -
Applied Biochemistry and Biotechnology Mar 2020The extensive use of chemical fungicide in the health and agriculture sectors has increased environmental concerns and promoted an extensive search for alternative...
Pyrrolnitrin from Rhizospheric Serratia marcescens NCIM 5696: Optimization of Process Parameters Using Statistical Tools and Seed-Applied Bioprotectants for Vigna radiata (L.) Against Fusarium oxysporum MTCC 9913.
The extensive use of chemical fungicide in the health and agriculture sectors has increased environmental concerns and promoted an extensive search for alternative bioactives from the microbial system. In the present study, two rhizospheric strains of Serratia spp. (TO-2 and TW-3) have been shown to secrete pyrrolnitrin (PRN) in the range of 11.35 to 35.97 μg ml using MSG and MSD medium after 72 h under static and shake conditions, respectively, but thereafter marginally declined in 96 to 240 h. Alternative one variable assortment at a time (OVAT) for PRN secretion by TW-3 yielded 59.27 μg ml using (gl) glycerol (20), monosodium glutamate (14), KHPO (14), NHCl (3), NaHPO (4), and MgSO (0.3) at pH 7, 120 rpm within 72 h. Further, the Placket-Burman Design (PBD) identified KHPO, glycerol, pH, and monosodium glutamate as significant variables and optimized by centered composite design. Accordingly, 3% glycerol, 1.72% KHPO, 1.1% monosodium glutamate, 0.4% NaHPO, 0.03% MgSO, 0.05% FeSO, and 0.01% ZnSO were found to enhance the yield of PRN to 96.54 μg ml by TW-3 in 72 h, 120 rpm. Thus, the statistical tool employed in the present study showed a threefold hike in PRN secretion over the OVAT approach, thereby indicating the scope for more PRN production from rhizobacteria. Further, seed application of low PRN (30 μg ml) concentration in treatments I and II showed > 90% germination in the initial seed germination and pot assay with the Fusarium oxysporum challenge compared to the control. Also, various growth parameters calculated during 11 days of experiment were significantly increased compared to the negative control (seed + fungus) in both treatments. Thus, the application of PRN at a low concentration to seeds of Vigna radiata (L.) offered protection against the phytopathogenic F. oxysporum MTCC 9913 challenge, suggesting biocontrol activity potential for use in agriculture soils particularly salt-affected soil.
Topics: Fungicides, Industrial; Fusarium; Pyrrolnitrin; Rhizosphere; Seeds; Serratia marcescens; Soil; Soil Microbiology; Vigna
PubMed: 31493159
DOI: 10.1007/s12010-019-03123-w -
The Journal of Antibiotics Aug 1982
Topics: Antifungal Agents; Chemical Phenomena; Chemistry; Fermentation; Myxococcales; Pyrrolnitrin
PubMed: 6815147
DOI: 10.7164/antibiotics.35.1101 -
Journal of Applied Microbiology Jul 1998A bacterial strain identified as Burkholderia cepacia NB-1 was isolated from water ponds in the botanical garden in Tübingen, Germany, and was found to produce a broad...
A bacterial strain identified as Burkholderia cepacia NB-1 was isolated from water ponds in the botanical garden in Tübingen, Germany, and was found to produce a broad spectrum phenylpyrrole antimicrobial substance active against filamentous fungi, yeasts and Gram-positive bacteria. In batch culture containing glycerol and L-glutamic acid, the isolate NB-1 produced the antibiotic optimally late in the growth phase and accumulated a main portion in their cells. Isolation and purification of the antibiotic from Burkholderia (Pseudomonas) cepacia NB-1 by acetone extraction, gel filtration on Sephadex LH-20 and preparative HPLC yielded 0.54 mg l-1 of a pure substance. Spectroscopic data (HPLC, MS and NMR) confirmed that the compound was pyrrolnitrin [3-chloro-4-(2'-nitro-3'-chloro-phenyl) pyrrole]. Pyrrolnitrin has an inhibitory effect on the electron transport system, as demonstrated by isolated mitochondria from Neurospora crassa 74 A. This inhibition was relieved by N,N,N',N'-tetramethyl-p-phenylenediamine dihydrochloride (TMPD), indicating that pyrrolnitrin blocked the electron transfer between the dehydrogenases and the cytochrome components of the respiratory chain. Among Gram-positive bacteria, pyrrolnitrin was most active against certain Streptomyces species, especially S. antibioticus, which has not previously been described in the literature. In the presence of pyrrolnitrin, aerial mycelium and spore formation of Strep. antibioticus was suppressed, although growth continued via substrate mycelium. The new findings of inhibition of streptomycetes and their secondary metabolism by pyrrolnitrin may contribute to the fact that Pseudomonas species predominate in soil and compete even with antibiotic-producing Streptomyces.
Topics: Antifungal Agents; Burkholderia cepacia; Chromatography, Gel; Chromatography, High Pressure Liquid; Mitochondria; Neurospora crassa; Pyrrolnitrin; Spores; Streptomyces; Tetramethylphenylenediamine; Water Microbiology
PubMed: 9721657
DOI: 10.1046/j.1365-2672.1998.00473.x -
Contact Dermatitis Jan 1982
Topics: Antifungal Agents; Dermatitis, Contact; Drug Eruptions; Humans; Infant; Pyrrolnitrin; Skin; Tinea
PubMed: 6461490
DOI: 10.1111/j.1600-0536.1982.tb04136.x -
PloS One 2015Pseudomonas chlororaphis strain PA23 is a biocontrol agent able to suppress growth of the fungal pathogen Sclerotinia sclerotiorum. This bacterium produces an arsenal of...
Pseudomonas chlororaphis strain PA23 is a biocontrol agent able to suppress growth of the fungal pathogen Sclerotinia sclerotiorum. This bacterium produces an arsenal of exometabolites including pyrrolnitrin (PRN), phenazine (PHZ), hydrogen cyanide (HCN), and degradative enzymes. Production of these compounds is controlled at both the transcriptional and posttranscriptional levels by the Gac-Rsm system, RpoS, PsrA, and the Phz quorum-sensing system. Beyond pathogen-suppression, the success of a biocontrol agent is dependent upon its ability to establish itself in the environment where predation by bacterivorous organisms, including nematodes, may threaten persistence. The focus of this study was to investigate whether PA23 is able to resist grazing by Caenorhabditis elegans and to define the role played by exoproducts in the bacterial-nematode interaction. We discovered that both PRN and HCN contribute to fast- and slow-killing of C. elegans. HCN is well-established as having lethal effects on C. elegans; however, PRN has not been reported to be nematicidal. Exposure of L4 stage nematodes to purified PRN reduced nematode viability in a dose-dependent fashion and led to reduced hatching of eggs laid by gravid adults. Because bacterial metabolites can act as chemoattractants or repellents, we analyzed whether PA23 exhibited attractant or repulsive properties towards C. elegans. Both PRN and HCN were found to be potent repellents. Next we investigated whether the presence of C. elegans would elicit changes in PA23 gene activity. Co-culturing the two organisms increased expression of a number of genes associated with biocontrol, including phzA, hcnA, phzR, phzI, rpoS and gacS. Exoproduct analysis showed that PHZ and autoinducer signals were upregulated, consistent with the gene expression profiles. Collectively, these findings indicate that PA23 is able to sense the presence of C. elegans and it is able to both repel and kill the nematodes, which should facilitate environmental persistence and ultimately biocontrol.
Topics: Animals; Antinematodal Agents; Biological Assay; Caenorhabditis elegans; Gene Expression Regulation, Bacterial; Hydrogen Cyanide; Oviposition; Pest Control, Biological; Pseudomonas; Pyrrolnitrin
PubMed: 25901993
DOI: 10.1371/journal.pone.0123184 -
Applied Microbiology May 1969The antifungal activity of pyrrolnitrin, previously shown to be effective against superficial infections, was evaluated against experimental systemic mycoses.... (Comparative Study)
Comparative Study
The antifungal activity of pyrrolnitrin, previously shown to be effective against superficial infections, was evaluated against experimental systemic mycoses. Pyrrolnitrin was inhibitory in vitro at <0.78 to 100 mug/ml to Candida albicans, Cryptococcus neoformans, Blastomyces dermatitidis, Sporotrichum schenckii, and Histoplasma capsulatum. Pyrrolnitrin activity was reduced about 90% in sera. After multiple subcutaneous doses of pyrrolnitrin at 20 mg/kg, activity was recovered in mouse blood and urine as well as kidney, liver, and brain homogenates. Multiple daily doses (50 mg/kg) of this antibiotic were effective in reducing by 74% the number of viable cells of C. albicans recovered from kidney homogenates. Multiple doses (15 mg/kg) resulted in a 74% reduction in the number of C. neoformans from brain homogenates. Pyrrolnitrin was ineffective in reducing the recovery of B. dermatitidis or H. capsulatum from liver or spleen homogenates of infected mice. When compared with amphotericin B, hamycin, 5-fluorocytosine, and saramycetin, this antibiotic was less effective. This study indicates that pyrrolnitrin would have limited usefulness as a systemic antifungal agent.
Topics: Amphotericin B; Animals; Antifungal Agents; Blastomyces; Blastomycosis; Blood; Candida; Candidiasis; Cryptococcosis; Cryptococcus; Histoplasma; Histoplasmosis; Mice; Neurospora; Sporothrix
PubMed: 5785951
DOI: 10.1128/am.17.5.690-694.1969 -
The Journal of Antibiotics Dec 1983The mutant strain ACN of Pseudomonas aureofaciens ATCC 15926 produces several bromo derivatives of pyrrolnitrin. Five brominated amino- and three brominated nitrophenyl...
The mutant strain ACN of Pseudomonas aureofaciens ATCC 15926 produces several bromo derivatives of pyrrolnitrin. Five brominated amino- and three brominated nitrophenyl pyrrole compounds could be isolated, and their structures were established by 1H NMR, UV and mass spectroscopy. The isolated amino compounds showed no biological activity; the nitro derivatives inhibited the growth of Neurospora crassa ATCC 9276, though not as effective as pyrrolnitrin itself. 2-Carboxy-4-(2-amino-3-bromophenyl)pyrrole (X) is demonstrated to be an intermediate in the biosynthesis of brominated pyrrolnitrin; the biosynthetic pathway to bromo derivatives of pyrrolnitrin is discussed.
Topics: Antifungal Agents; Chromatography, High Pressure Liquid; Mass Spectrometry; Pseudomonas; Pyrrolnitrin; Spectrophotometry, Ultraviolet; Structure-Activity Relationship
PubMed: 6662814
DOI: 10.7164/antibiotics.36.1735